Dry eye treatment systems

ABSTRACT

Dry eye treatment apparatus and methods are described herein which generally comprise a patch or strip affixed to the skin of the upper and/or lower eyelids to deliver heat or other forms of energy, pressure, drugs, moisture, etc. (alone or in combination) to the one or more meibomian glands contained within the underlying skin. The treatment strip or strips include one or more strips configured to adhere to an underlying region of skin in proximity to one or both eyes of a subject such that the one or more strips allow for the subject to blink naturally without restriction from the one or more patches. Moreover, the one or more strips may be configured to emit energy to the underlying region of skin and where the one or more strips are shaped to follow a location of one or more meibomiam glands contained within the underlying region of skin.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation-in-part of U.S. patent application Ser. No.13/343,407 filed Jan. 4, 2012, which is incorporated herein by referencein its entirety.

FIELD OF THE INVENTION

The present invention relates to methods and apparatus for treatment ofdry eye syndrome and other related conditions. More particularly, thepresent invention relates to methods and apparatus for the treatment ofdry eye syndrome using adhesive strips which are specifically contouredor shaped to adhere to selected regions around a patient's eyes orperi-orbital region.

BACKGROUND OF THE INVENTION

Tears are a complex mixture of water, lipids, mucus, proteins andelectrolytes and this mixture helps to maintain a smooth and clearoptical surface and also helps to protect the eyes from infection. Thetear film has three basic layers: oil, water, and mucus and problems ordisturbances in any of these layers can cause dry eyes symptoms.

The outermost layer of the tear film is typically comprised of an oillayer containing fatty acids and lipids (meibum) which are producedprimarily by sebaceous glands called the meibomian glands located alongthe eyelid margin. The oil layer smoothes the tear surface and slowsevaporation of the watery middle layer. However, if the meibomian glandsfail to produce enough oil, produce suboptimal fatty acid mixtures, orif the glands become obstructed or clogged, the watery layer typicallyevaporates too quickly causing dry eyes. A blockage of the meibomianglands can lead to enlarged glands or infections. Dry eyes are thuscommon in people whose meibomian glands are obstructed or functioningimproperly.

The middle layer of tears is composed primarily of an aqueous solution,which is produced by the lacrimal glands (tear glands). The middle layercleanses the eyes and washes away foreign particles or irritants,maintains a clear optical medium, and keeps the ocular surface moist.The innermost layer of the tear film is composed primarily of mucuswhich helps to spread the tears evenly over the surface of the eyes. Alack of mucus in the tear film is also associated with dry eye syndrome.

As discussed above, the meibomian glands are oil-secreting glandslocated within both the upper and lower eyelids. There are approximately30 to 40 glands along the upper eyelid and approximately 20 to 30 glandsalong the lower eyelid with the ducts for each of the glands openingalong the inner edge of the free margin of the respective lids by minuteforamina through which their secretion is released to prevent the lidsadhering to each other. An example of the location of the meibomianglands is illustrated in the cross-sectional view of the upper eyelid ULshown in FIG. 1A which illustrates the relative positioning of a singlemeibomian gland MG. Other glands and anatomical features are illustratedfor reference, e,g., the glands of Wolfring GW, tarsus TR, gland of MollGM, gland of Zeis GZ, gland of Krause GK, upper fornix UF, conjunctivaCN and cornea CR of the eye which is partially covered by the uppereyelid UL. As illustrated, the meibomian gland MG is positioned along alength of the upper eyelid UL (and lower eyelid LL) with the ductopening along the inner edge of the eyelid UL in proximity to a surfaceof the underlying eye.

FIG. 1B illustrates a front view of a patient's eye having the uppereyelid UL and lower eyelid LL in a closed position, such as when thepatient blinks. As shown, the meibomian glands MG may be seen alignedadjacent to one another over both the upper UL and lower eyelids LL.FIG. 1C also shows a perspective view of a patient's eye in the openposition to illustrate how the meibomian glands are typically alignedrelative to one another when the patient's eye is opened.

Blinking is thought to be the primary mechanism to open the orifice ofthe meibomian glands to allow for the release of oil secretions from theglands. The natural blinking motion and blinking force causes the upperlid to pull a sheet of the lipids secreted by the meibomian glands overthe two underlying layers of the tear film thus forming the protectivecoating which limits the rate at which the underlying layers evaporate.it is estimated that approximately 65% of meibomian gland disease or dryeye results from a defective lipid layer or an insufficient quantity ofsuch lipids that results in accelerated evaporation of the aqueouslayer. Hence, blinking disorders, or other disorders that affect propertear distribution, may also cause or exacerbate meibomian glanddysfunction or dry eye.

As the eyelids close in a total blink, the superior and inferiorfornices, which hold a reservoir of tears, are compressed by the forceof the preseptal muscles and the eyelids move toward one another. Theupper eyelid, for instance, moves over the eye while exerting upon theeye surface a force which helps to clear the front of the eye of debris,insoluble mucin, and also expresses the oil secretions from themeibomian glands. The lower lid moves horizontally in the nasaldirection and pushes debris toward both punctae, the openings thatultimately drain into the nasal cavities.

As the eyelids open the tear film is redistributed where the upper lidpulls the aqueous phase via capillary action and the lipid layer spreadsas quickly as the eyelids move. Hence, eyelid movement is accordinglyimportant in tear-film renewal, distribution, turnover, and drainage.

For a variety of reasons, the meibomian glands can become blocked,plugged, or occluded resulting in meibomian gland dysfunction and dryeye disease. The obstruction that triggers the disease can occuranywhere within the meibomian gland, for instance, at the gland'ssurface, or orifice preventing normal lipid secretions from flowing; inthe main channel of the gland which may be narrowed or blocked; or inother locations deeper within the gland that lead to the main channel.

Treatments for blocked meibomian glands may include a numberconventional treatments. One course of treatment includes theapplication of soap and cleaning agents, eyelid scrubs, or antibioticsto reduce eyelid inflammation. Antibiotics such as tetracycline,doxycycline, metronidazole, or erythromycin can be administered orallyor topically to help regulate or improve meibomian gland lipidproduction. Inflammation on the surface of the eye may also becontrolled with topical drugs such as corticosteroids or cyclosporine(RESTASIS®, Allergan, Inc., CA), or other anti-inflammatory compounds orimmune-suppressants. Evidence suggests that ocular surface inflammationis not only associated with meibomian gland dysfunction but also withdry eye syndrome.

Other examples of dry eye treatments may include the application ofprescription eye inserts for people with moderate to severe dry eyessymptoms who are unable to use artificial tears. An eye insert, e.g.,hydroxypropyl cellulose (LACRISERT®, Merck & Co., Inc., NJ), may beinserted between the lower eyelid and eye. The insert dissolves slowlyto release a substance which lubricates the eye. Alternatively, specialcontact lenses may be used to shield the surface of the eye to trapmoisture.

In other treatments, the patient's tear ducts may be closed to preventthe tear film from draining away from the surface of the eye too quicklyby procedures such as insertion of punctal plugs into the tear ducts orcauterizing the tissues of the drainage area. Aside from implants orcauterizing treatments, dry eye syndrome may be treated using,pharmaceutical agents such as eyedrops, ointments which coat the eyes,etc. Artificial tears, gels, ointments, autologous serum tears, oralbumin drops have all been employed in the treatment of dry eye.

Additionally, warm compresses are also typically placed over the eyesand are used to restore function to the meibomian glands by melting, anylipid plugs as well as incorporating massaging of the lids which mayfurther express meibomian gland contents. However, application of warmcompresses require their application two to three times daily duringwhich time patients may incorrectly target only one of the affected lidsand are also prevented from seeing out of the treated eye because of thecompresses. Compresses may be too hot, further exacerbatinginflammation, or they may cool too quickly preventing adequatetherapeutic effect.

Other treatment devices have also been developed which cover the entireaffected eye to apply heat and a massaging force directly to theaffected eyelids. However, such devices, like the compresses, requirethat the patient's eyes be temporarily but completely obstructed duringthe treatment resulting in discomfort, lost productivity, andpotentially lower compliance among patients. Additionally, thesetreatments require visits to a physician or healthcare provider and arenot as well-suited for widespread consumer adoption.

Accordingly, there exists a need for methods and apparatus which arerelatively simple to routinely use for the patient, which also allow forthe patient to continue their normal activities, is non-obtrusive andnon-disruptive, and which also take advantage of the patient's naturalphysiological activities to facilitate treatment.

SUMMARY OF THE INVENTION

In treating conditions such as meibomian gland dysfunction or dry eyesyndrome, a patch or strip can be affixed to the skin of the upperand/or lower eyelids to deliver heat or other forms of energy, pressure,drugs, moisture, etc. (alone or in combination) to the one or moremeibomian glands contained within the underlying skin. In particular,the assembly for the treatment strip or strips may generally compriseone or more strips configured to adhere to an underlying region of skinin proximity to one or both eyes of a subject such that the one or morestrips allow for the subject to blink naturally without restriction fromthe one or more patches. Moreover, the one or more strips may beconfigured to emit energy to the underlying region of skin and where theone or more strips are shaped to follow a location of one or moremeibomian glands contained within the underlying region of skin.

In use, the one or more strips may be adhered to a region of skin inproximity to one or both eyes of a subject such that the one or morestrips allow for the subject to blink naturally without restriction fromthe one or more patches. While adhered, the strips may emit energy tothe region of skin, where the one or more strips are shaped to follow alocation of one or more meibomian glands contained within the region ofskin. Alternatively, while the strip may not directly overly a meibomianor other ocular or orbital gland, it may deliver energy or absorb energyfrom underlying neighboring vasculature which ultimately supplies saidglands. In other words, heating or cooling the blood supply to theeyelids, meibomian glands, and/or lacrimal glands using these strips mayaffect their function and metabolism while not necessarily needing todirectly overly them in particular variations.

The upper strip may thus have an upper curved or arcuate periphery whichis shaped to extend and follow the upper (or superior) border of themeibomian glands (such as along or up to the upper eyelid crease) whilethe straightened periphery of the lower edge may be shaped to extend andfollow the lower (or inferior) border of the meibomian glands such asalong the free margin of the upper eyelid. Although straightened, thelower edge may be gently curved or arcuate in alternative variations.The lower strip may similarly have an upper straightened periphery toextend and follow the upper (or superior) border of the meibomian glandsalong the free margin of the lower eyelid and a lower curved or arcuateperiphery to extend and follow the lower (or inferior) border of themeibomian glands along the lower eyelid (such as along or up to thelower eyelid crease). Alternatively, the upper periphery of the lowerstrip may also be gently curved or arcuate in alternative variations aswell.

In other words, with the tarsal plate containing, the meibomian glandswhich span from proximal to distal, the peripheral edges of thetreatment strips may correspond to the distal eyelid margin and proximalperipheral edge and the treatment strips can assume multipleconfigurations. Generally, the peripheral distal edge of the treatmentstrip may be relatively straight or assume a gentle curve either ofwhich can follow the underlying distal eyelid margin and tarsal platewhile having a proximal peripheral edge that is relatively curved toassume the more curved proximal edge of the underlying tarsal plate.

The strips may be used individually for placement upon only the uppereyelid or only the lower eyelid depending upon the desired treatmentMoreover, the lengths of the treatment strips may also he varied totarget individual meibomian glands for providing a targeted treatment,if desired, and as described in further detail herein. Additionally,while the treatment strips may be sized generally, they may also becustom made or sized for a specific individual's eyelid dimensions.

Because of the specific contoured sizes and flexibility of the treatmentstrips the treatment strips may be placed upon the patient to applytherapy to the underlying meibomian glands allowing the patient's eyesto be opened and closed normally without interference from one or bothtreatment strips. Accordingly, the treatment strips contoured size,shape, and flexibility allow for treatment to occur while also allowingfor the patient to have one or both eyes remain opened such that normal,physiologic blinking can proceed during the course of treatment. Ratherthan relying on an application of any type of external force, thetreatment strips take advantage of the eye's natural mechanism forclearing oil from the meibomian glands via blinking. Hence, thetreatment strips may be adhered in place for treatment without anyfurther intervention by the patient, or healthcare provider such thatthe treatment strips may apply, e.g., heat energy, to melt or liquefyany waxy or solid meibomian gland obstructions while the eyes remainunobstructed and are allowed to blink naturally. The treatment stripsthus allow for the natural blinking force to clear the glands of theheat-treated softened obstructions before they have re-solidified unlikeother treatments which require that the patient keep their eyes dosed orobstructed during the course of a treatment and prevent or inhibit thepatient from blinking.

The treatment strip may be configured to have a contact layer (e.g.,fabricated from conductive materials such as metals, alloys, porousceramics, engineering ceramics, woods, polymers, composites, foams,polymer foams, fabrics, elastomers, etc.) which may protect the skinfrom burns or any other adverse effects. A second heating layer may bepositioned above the contact layer (or directly in contact against theskin) for generating the heat energy and an insulative layer may bepositioned atop the heating layer for focusing, directing, or reflectingthe heat towards the underlying skin surface as well as to protect thepatient from contact with the heating layer from other parts of thebody. The insulative layer may accordingly be fabricated from a varietyof insulative materials, e.g., foams, foam tapes, gauze, silicone,microporous polyethylene films, fabrics, polymers, etc.

Although the application of heat energy from the treatment strips isdescribed, other variations may alternatively include the application ofusing the treatment strips for cooling of the underlying skin. Ratherthan using the heating layer in an exothermic reaction, the layer may beconfigured to utilize an endothermic reaction instead to provide forcooling of the skin. Cooling, rather than heating, may be applied forconditions such as reducing inflammation, alleviating allergies or tiredeyes, etc. particularly as the patient rests or sleeps.

Aside from the application of heat energy from the treatment strips, thestrips may also include a layer for the diffusion or release of one ormore pharmaceutical, biological, or chemical agents either alone or incombination with the heat treatment. For instance, the pharmaceutical,biological, or chemical agents may be incorporated into the either thecontact layer, insulative layer, or in a separate layer entirely, fortransdermal delivery to the meibomian glands or to the areas surroundingthe meibomian glands for additional and/or alternative treatments. Inthe event that the pharmacological or chemical agent is released duringthe heat treatment, the heat may help to improve penetration of anydrugs into the underlying skin.

While the treatment strips may incorporate various layers into thestrips to effect various different treatments, the strips may also bevaried in size, shape, contour, etc. depending upon the desiredtreatment areas so long as the treatment strips are contoured or shapedto follow the location of at least one meibomian gland.

While the treatment strips may be applied to one or more of themeibomian glands, variations of the strip may also be used to treatother glands such as the sebaceous glands, e.g., for acne treatment.Treatment strips used to treat acne may utilize differentpharmacological treatments. Moreover, the treatment strips may be usedto potentially treat eye disorders beyond meibomian gland dysfunction.

Yet another example may include use of the treatment strips fortreating, disorders of the lacrimal gland and/or palpebral lacrimalgland which are located above the eye. Variously sized treatment strips,such as lacrimal gland strips which are sized to have a curved upperperiphery, may be sized for placement directly over the skin surfaceabove where the lacrimal glands are located. The lacrimal glands and/orpalpebral lacrimal gland may be treated alone or in combination with thetreatment strips contoured for treatment of the meibomian glands.

While the treatment strips may be applied over the meibomian glands toapply the heat energy, the treatment does not require the application ofany external force applied by the strip or any other external device butmay utilize the natural blinking of the patient to facilitate treatment.However, in additional variations, the treatment strips may beconfigured to apply both the heat treatment as well as an externalforce. Any number of mechanisms may be utilized to apply a pinching orbiasing force to provide for compression of the underlying skin and ofthe meibomian glands during application of the heat therapy.

Aside from a compression force, the strip may be formed with alternativecomponents such as a mechanical component to impart vibrational energyor other forms of energy to facilitate the expression of the meibomianglands and promote oil secretion.

In yet another variation, one or both treatment snips may be configuredto incorporate an indicator, e.g., LED light, alarm, vibration element,etc., electrically coupled to a power supply and/or processor to alertthe patient when a prescribed treatment has been completed. This feature(and any of the other features) may be combined with any of the othervariations of the treatment strips described, herein as practicable.

With the incorporation of a processor in to the treatment strips,treatment times or other parameters such as temperature of the stripsmay be programmed and optionally shut on or off selectively by thepatient or automatically. Moreover, other parameters such as thefrequency of the heat delivery or other stimulation may also beprogrammed by the processor to provide further flexibility in treatment.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a cross-sectional side view of an upper eyelid and anexample of the location of a meibomian gland.

FIG. 1B shows a front view diagram of meibomian gland distribution inhuman eyelids having the upper eyelid and lower eyelid in a closedposition, such as when the patient blinks, and the alignment of themeibomian glands over both the upper and lower eyelids.

FIG. 1C shows a perspective view of a patient's eye in the open positionto illustrate how the meibomian glands are typically aligned relative toone another when the patients eye is opened.

FIG. 2A shows a front view of a patient's eye in a closed position withan example of treatment strips which adhere onto the upper or lowereyelids (or both) and where the strips are sized or contoured forplacement directly over the meibomian glands located in the underlyingeyelids.

FIG. 2B shows the treatment strips of FIG. 2A illustrating how thestrips may remain adhered to the patient skin while allowing for theeyelids to retract and allow for the patient to continue blinking whileviewing normally out of the eye. While the strips may be applied fromeyelid margin to eyelid crease, they may alternatively flex or accordionand/or compress during blinks to prevent impairment of normal blinkingand maximize comfort.

FIG. 3A shows an example of a contoured treatment strips.

FIG. 3B shows an example of a cross-sectional side view of a treatmentstrip.

FIG. 3C shows another variation of a treatment strip which mayoptionally incorporate a controller.

FIG. 3D shows yet another variation where a treatment strip may bethrilled into a zig-zag or curved configuration to facilitate theblinking by the patient.

FIG. 4 shows a front view of another variation of the treatment stripwhich relatively thin and positioned over the upper eyelids.

FIG. 5 shows a front view of another variation of the treatment stripwhich is relatively thick for treatment of the targeted meibomian glandsas well as the surrounding tissue.

FIG. 6 shows a front view of another variation of the treatment stripwhich is contoured to more closely follow the meibomian glands in theupper eyelids.

FIG. 7 shows a front view of another variation of the treatment stripwhich may be formed into shortened strips for selective placement alongthe eyelids.

FIG. 8 shows a front view of another variation of the treatment stripwhich is relatively thin and contoured for placement along the lowereyelids.

FIG. 9 shows a front view of another variation of the treatment stripwhich is relatively thicker and also contoured for placement along thelower eyelids.

FIG. 10 shows a front view of another variation of the treatment stripwhich is relatively thick for placement along the lower eyelids.

FIG. 11 shows a front view of another variation of the treatment stripwhich is contoured for the lower eyelids and which may be shortened intovarious lengths.

FIG. 12 shows a front view of another variation of the treatment stripwhich is relatively straightened and selectively shortened.

FIG. 13 shows a front view of another variation of the treatment stripwhich is contoured and further illustrates how differently sized stripsmay be used in combination with one another.

FIG. 14 shows a front view of another variation of the treatment stripwhich is sized to follow not only the meibomian glands along the lowereyelid but also the surrounding tissue regions.

FIG. 15 shows a front view of another variation of the treatment stripwhich is contoured to follow the meibomian glands along the lower eyelidalong with the surrounding tissue regions.

FIG. 16 shows a front view of yet another variation where the strip iscontoured to follow at least a portion of the meibomian glands but alsoto cover selected regions of the surrounding tissue.

FIG. 17 shows a front view of yet another variation which is contouredto selectively treat particular regions of the underlying tissue.

FIG. 18 shows a front view of yet another variation where the contouredtreatment strips may be used in combination for treating both upper andlower eyelids.

FIG. 19 shows a front view of yet another variation where the treatmentstrips may be altered in color to more closely match the underlying skintone.

FIG. 20 shows a front view of yet another variation where the treatmentstrips may be sized to treat specified meibomian glands.

FIG. 21 shows a front view of yet another variation where the strips maybe varied in size to selectively treat particular meibomian glands.

FIG. 22 shows a front view of yet another variation where the treatmentstrips may be sized to treat individual meibomian glands.

FIG. 23 shows a front view of yet another variation where the treatmentstrips may be sized for placement along the lower eyelids.

FIG. 24 shows a front view illustrating the relative positioning of thelacrimal glands.

FIGS. 25 to 27 show variations of treatment strips which may becontoured and positioned for treating the underlying lacrimal glands.

FIGS. 28 to 30 show variations of treatment strips which may becontoured and sized for treating the meibomian glands in combinationwith optionally treating the lacrimal glands as well.

FIGS. 31 and 32 show variations on treatment strips which may be sizedfor selectively treating particular meibomian glands in combination withthe lacrimal gland.

FIG. 33 shows another variation of a treatment strips which may havemechanically biasing features incorporated along the strips for applyinga force to the underlying tissue and meibomian glands.

FIG. 34 shows it detail perspective view of the treatment strip of FIG.33 illustrating an example of biasing mechanisms incorporated along thestrips.

FIG. 35 shows another variation of treatment strips incorporating one ormore transducers for imparting a vibrating force to the underlyingtissue and meibomian glands.

FIG. 36 shows yet another variation of treatment strips incorporatingelectrodes through the length of the strips.

FIG. 37 shows yet another variation of treatment strips incorporatingmicrowave antennas alone the strips.

FIG. 38 shows yet another variation of a treatment strip incorporating atimer and indicating for alerting a user when a treatment has beencompleted.

FIG. 39 shows yet another variation of an eyelid treatment system whichmay be coupled to a portable remote controller such as a smartphone ortablet.

DETAILED DESCRIPTION OF THE INVENTION

In treating conditions such as meibomian gland dysfunction (MGD), whichis commonly associated with the evaporative form of dry eye syndrome(DES), a patch, strip or thin adhesive device can be affixed to the skinof the upper and/or lower eyelids to deliver heat or other forms ofenergy, pressure, drugs, moisture, etc. (alone or in combination) to theone or more meibomian glands contained, within the underlying, skin. Inparticular, the treatment strip or strips may be configured and sizedspecifically for placement over one or more targeted meibomian glandscontained within the skin of the upper and/or lower eyelids. Theapplication of thermal therapy, e.g., heating or cooling, can cross theeyelids quite easily as the eyelids are generally the thinnest skinfound on the human body and the tissue is highly vascularized. With theroot of the eyelid located proximally and the eyelid margin locateddistally, the net arterial flow of blood flows from proximal to distal.So wherever these treatment strips are placed, the heating or coolingtherapy may easily he carried throughout the eyelid and any structurescontained therein, e.g., meibomian glands MG, lacrimal glands LG, glandof Zeis GZ, gland of Moll GM, gland of Wolfring GW, gland of Kraus GK,etc.

Moreover, because the eyelid is so thin, the beating or cooling therapycan be transmitted to the ocular surface and the eye itself (describedin further detail below). Thus, the therapy can impart energy to theconjunctiva, goblet cells, episcleral vasculature, cornea, aqueoushumor, iris, ciliary body, and possibly the anterior vitreous and lens.Thus, any thermal therapy by the treatment strips may also impact and beused to treat ocular surface disorders and anterior segment diseases,e.g., conjunctivitis, keratitis, keratopathy, iritis, cyclitis,glaucoma, cataract, etc. Also, there may be use in the postoperativestate-like after LASIK, PRK, or cataract or corneal surgery or otherocular, peri-ocular, intraocular, or eyelid surgery, as described infurther detail below.

As shown in the front view of FIG. 2A, one variation of such treatmentstrips may be seen as being adhered temporarily upon the upper eyelid ULand lower eyelid LL over an eve of a patient P when closed forillustrative purposes. The contoured upper strip 10 may he sized foradherence directly upon the skin of the upper eyelid UL such that thestrip 10 has a configuration and shape which follows the location of theone or more meibomian glands contained within the underlying, skin ofthe upper eyelid UL. Likewise, the contoured lower strip 12 may alsohave a configuration and shape which follows the location of the one ormore meibomian glands contained within the underlying skin of the lowereyelid LL. In other variations, the contoured strip may stop at theeyelid crease or cross over it as described in other variations below.

The upper strip 10 may thus have an upper curved or arcuate periphery 14which is shaped to extend and follow the upper (or superior) border ofthe meibomian glands (such as along or up to the upper eyelid crease)while the straightened periphery 16 of the lower edge may be shaped toextend and follow the lower (or inferior) border of the meibomian glandssuch as along the free margin of the upper eyelid UL. The lower strip 12may similarly have an upper straightened periphery 20 to extend andfollow the upper (or superior) border of the meibomian glands along thefree margin of the lower eyelid LL and a lower curved or arcuateperiphery 18 to extend and follow the lower (or inferior) border of themeibomian glands along the lower eyelid LL (such as along or up to thelower eyelid crease). The use of the terms lower and upper herein referto the periphery of the treatment strips when placed upon the patient P(human or animal) and are used herein for descriptive purposes.

While the treatment strips 10, 12 are both shown adhered upon therespective upper eyelid UL and lower eyelid LL, the strips 10, 12 may beused individually for placement upon only the upper eyelid UL or onlythe lower eyelid LL depending upon the desired treatment. Moreover, thelengths of the treatment strips 10, 12 may also be varied to targetindividual meibomian glands for providing a targeted treatment, ifdesired, and as described in further detail herein.

While the treatment strips 10, 12 are shown placed upon the closedeyelids of the patient P, the strips 10, 12 are arc-shaped or flexibleenough to assume the curvature of the patient's eyelid margin and may belong enough to cover some or all of the underlying meibomian glands inthe tarsal plate. While the treatment strips 10, 12 may be sizedgenerally, they may also be custom made or sized for a specificindividual's eyelid dimensions or shaped to optimize adhesion and/orcomfort and/or stability. Generally, the treatment strips 10, 12 mayhave a length anywhere from about 1 mm to 50 mm depending upon thedesired treatment length as well as the anatomical considerations of thepatient since the typical palpebral fissure length in an adult is about27 mm to 30 mm. Thus, to cover as many as all of the meibomian glands,the treatment strips 10, 12 may be sized to have length of e.g., 25 mmto 30 mm, or if sized to cover just beyond all the meibomian glands, alength of e.g., 30 mm to 50 mm (or more if needed to optimizeadhesion/comfort/stability). Moreover, one or both treatment strips 10,12 can have a width ranging anywhere from about 1 mm to 25 mm since thetypical eyelid crease in a Caucasian male is about 8 mm to 9 mm abovethe eyelid margin while in Caucasian females it is about 9 mm to 11 mmabove the eyelid margin (or more if needed for adhesion/comfort andpotentially increased efficacy from heating or cooling the inbound bloodflow). Customization enables it to fit any particular anatomy, race,ethnicity, etc. Moreover, the treatment strips may be manufactured withvarying levels of flexibility to accommodate the ergonomics of theeyelid and eyelid blink for optimal comfort and minimal obtrusiveness ormovement.

Because of the specific contoured sizes and flexibility of the treatmentstrips 10, 12, the treatment strips may be placed upon the patient P bythe patient himself/herself for consumer use or by a healthcare providerto apply therapy to the underlying meibomian glands allowing thepatient's eyes to be opened and closed normally, as shown in FIG. 2B,without interference from one or both treatment strips. While the stripsmay he applied from eyelid margin to eyelid crease, they mayalternatively flex or accordion and/or compress during blinks to preventimpairment of normal blinking and maximize comfort.

Typical treatment patches, such as for application of a warm compress,are generally sized for placement over the entire eye or eyes such thatthe patient is unable to open their eyes or blink during a treatmentsession. Yet, because of the strong association between DES and MGD (forinstance, MGD includes the spectrum of MGD, meibomitis, blepharitis, andocular rosacea), natural blinking by an individual is the mechanism bywhich meibomian gland secretions are normally released onto the eyelidmargin and over the tear. In the absence of blinking the oil containedwithin the meibomian glands remain unexpressed within the glands'terminal ducts and fail to contribute to distribution of the oily layerupon the tears.

Accordingly, the treatment strips 10, 12 contoured size, shape, andflexibility allow for treatment to occur while also allowing for thepatient to have one or both eyes remain opened such that normal,physiologic blinking can proceed during the course of treatment. Ratherthan relying on an application of any type of external force to expressthe oil or obstruction from the glands, the treatment strips 10, 12 takeadvantage of the eye's natural mechanism for clearing oil from themeibomian glands via blinking. Hence, the treatment strips 10, 12 may beadhered in place for treatment without any further intervention by thepatient or healthcare provider such that the treatment strips 10, 12 mayapply, e.g., heat energy, to melt or liquefy any waxy or solid meibomiangland obstructions while the eyes remain unobstructed and are allowed toblink naturally. The treatment strips 10, 12 thus allow for the naturalblinking to clear the glands of the heat-treated softened obstructionsbefore they have re-solidified unlike other treatments which requirethat the patient keep their eyes closed or obstructed during the courseof a treatment and prevent or inhibit the patient from blinking.Delivery of heat may also increase blood flow by promoting vasodilationas increased delivery of blood can affect metabolism, temperature ofother tissues, may have effects on inflammation, and can thereby improvetissue function.

Because some patients have obstructions or occlusions in their meibomianglands that may not sufficiently melt, loosen, or soften withoutattaining heightened temperatures at the meibomian glands, the treatmentstrips 10, 12 may apply heat or other treatments to the surface of theeyelids for a significant period of time for relatively longer treatmenttimes and at higher treatment temperatures because of the ability of thetreatment strips 10, 12 to remain attached to the patient during anygiven period throughout the day. Patients can assume their dailyactivities with their eyes open and eyes blinking and with the comfortof a strip-based treatment. Moreover, patients can affix the treatmentstrips as many times as needed throughout the day, week, month. etc.until dry eye symptoms subside. This increases the frequency oftreatment, convenience of treatment, and thus efficacy of treatment.

Because of the prolonged, treatment times, the application of a separateforce beyond the application of the strips may not be needed so long asthe patient is able to continue blinking during the course of treatment.Moreover, the treatment frequency may be varied depending upon theseverity of the condition to be treated. One example for potentialtreatment frequency may include application of one or both strips, e.g.,up to six times per day for ten minutes or up to an hour or more foreach treatment. Moreover, because the treatment strips are positionedover the meibomian glands which overlie the ocular surfaces, theapplication of the heating therapy may also indirectly heat the ocularsurface as well and may further reduce any chronic ocular surfaceinflammation, chronic conjunctival inflammation, or cornealneovascularization.

Aside from heating of the ocular surface, heat therapy may alsooptionally be used to potentially provide for indirect heating throughthe ocular surface as well for heating of the retina to provide athermal therapy to limit inflammation and neovascularization which areunderlying conditions for diseases such as Wet age-related maculardegeneration (AMID) and Diabetic Retinopathy.

While the treatment strips 10, 12 may be used throughout the day to takeadvantage of the patient's physiologic blinking, the treatment strips10, 12 may also be used while the patient is resting or sleeping orwhile the patient simply maintains their eyes closed.

The treatment strips 10, 12 are desirably flexible enough to accommodatemovement of the upper eyelid UL and/or lower eyelid LL which may move asmuch as about 15 mm or more. Thus, the treatment strips 10, 12 may befabricated from various materials. FIGS. 3A and 3B show front andcross-sectional side views, respectively, in one example of a treatmentstrip configured to have an adhesive 32 positioned about a periphery ofthe strip to leave a contact region 30 for direct placement against theskin surface. The contact region 30 may further include a moisturizinglayer to interface between the strip and skin to facilitate heattransfer from the strip as well as to provide moisturizing therapy tothe skin. Alternatively, the treatment strips may be used with anynumber of moisturizing agents which may be applied to the underlyingskin by the patient P or by a practitioner separately from the treatmentstrips. Moreover, the contact region 30 may be formed to have a surfacewhich is smooth, porous, irregular, corrugated, etc to facilitatecontact and transfer of the heat from the treatment strip to the skinsurface. Alternatively, the entire contact region 30, including itsperiphery, may be adhesive to maintain good contact. It may be hinged orcurved to allow flexing or accordion-like dynamic movement for comfortand better, physiologically-sound ergonomics. In use, the strip may beapplied under tension, as shown by the tensioned strip 10′ in FIG. 3D,to further reduce ally impairment to blinking and once adhered to theskin the strip may be released to allow for its flexion, as shown by thereleased strip 10″ also in FIG. 3D, to facilitate blinking by thepatient P.

In this variation, the treatment strip 10 may be configured to have acontact layer 34 (e.g., fabricated from conductive materials such asmetals, alloys, porous ceramics, engineering ceramics, woods,polymers_(:) composites, foams, polymer foams, elastomers, etc.) whichmay protect the skin from burns or any other adverse effects. A secondheating layer 36 may be positioned above the contact layer 34 (ordirectly in contact against the skin) for generating the heat energy andan insulative layer 38 may be positioned atop the heating layer 36 forfocusing, directing, or reflecting the heat towards the underlying, skinsurface as well as to protect the patient from contact with the heatinglayer 36 from other parts of the body. The insulative layer 38 mayaccordingly be fabricated from a variety of insulative materials, e.g.,foams, foam tapes, gauze, silicone, microporous polyethylene films,metals, alloys, reflective materials, mirrors, etc. Moreover, thethickness of the treatment strip 10 may vary, e.g., anywhere from about1/64″ to ⅛″ or more, depending upon the heating layer 36 mechanism aswell as the desired thermal profile and targeted transmissiontemperature. Additionally and/or alternatively, the insulative layer 38may be comprised of a thermochromic material which may change its colorwhen a targeted temperature has been reached by the treatment strip 10to indicate to the patient that the targeted temperature has beenachieved or when the therapy has been completed.

The heating layer 36 may be configured to generate its heat energy,e.g., up to a temperature range of about 20° to 55° C. (or more) orbetween 40° to 50° C., through any number various mechanisms such asmechanical, electrical, or chemical mechanisms. In one variation, theheating layer 36 may comprise an air-activated warmer that can increaseto an elevated treatment temperature for a period of time lasting, e.g.,from 5 minutes up to 24 hours or even longer. An example can include airactivated layer incorporating, e.g., iron. Other examples mayincorporate a heating layer 36 containing, e.g., cellulose, iron powder,water, activated carbon (to speed up reaction), vermiculite (waterreservoir), and salt (catalyst), saw dust, sodium chloride and water,etc. to generate heat from an exothermic oxidation of iron when exposedto air. Other variations may comprise a heating layer 36 whichincorporates light-based activation (visible or UV-light powered) or useof a supersaturated solution (crystallization-type) to initiate and/ormaintain an exothermic reaction.

Optionally, aside from use of a thermochromic material to determine whenthe treatment strip has reached a particular temperature, a separatetemperature sensor 39 (e.g., thermocouples or thermistor devices) may beincorporated onto the treatment strip 10, as shown in FIG. 3B, attachedeither to the top of the strip or to the bottom of the strip. Thetreatment strip 10 may also incorporate an optional controller and/ordisplay 37 having a processor which may be programmable and which mayincorporate a separate on/off feature, as shown in FIG. 3C. Thetemperature sensor 39 may be in communication with the controller 37which may be programmed to regulate the temperature of the heating layer36 and/or a length of time for a particular treatment. The controller 37may accordingly be programmable by a physician or caregiver or directlyby the patient. Alternatively, the controller 37 may be configured to beinaccessible by the patient but may merely provide temperature and/ortime indications for display to the patient. In the event that thecontroller 37 is programmable, the controller 37 may be programmed,e.g., to set a length of a heating, period, set treatment times, setpredetermined temperature ranges, control a heating temperature profile(such as gradually increasing the heating temperature or decreasingtemperature over a predetermined period of time), etc.

In another variation, the heating layer 36 may generate heat throughexothermic crystallization of supersaturated solutions (typically sodiumacetate) which are usually reusable. The treatment strips may berecharged by heating them, e.g., by boiling, and allowing them to cool.Heating of these treatment strips may triggered by snapping, a smallmetal device buried in the treatment strips which generates nucleationcenters that initiate crystallization. Heat is required to dissolve thesalt in its own water of crystallization and it is this heat that isreleased when crystallization is initiated.

In yet another variation, the heating layer 36 may comprise a batteryoperated warmer which utilizes electrically resistive heating elementsthat are used to convert electrical energy in the battery to thermalenergy. The power supply may be internal or external to the treatmentstrips and the treatment strips may charged, e.g., by direct electricalcontact, induction, etc.

Other mechanisms which may be incorporated into the heating layer 36 maycomprise chemically actuated reactions such those used by sodium acetateheating pads. For instance, a single-use chemical reaction utilizing thecatalyzed rusting of iron or dissolving calcium chloride may be usewhere the reagents are maintained in separate compartments within thetreatment strips. When the patient squeezes the treatment strips, thecompartments may break and the reagents mixed to produce heat. Examplesmay include use of a supersaturated solution of sodium acetate(NaCH₃COO) in water where crystallization may be triggered by flexing asmall flat disc of notched ferrous metal embedded in the liquid whichact as nucleation sites for the crystallization of the sodium acetateinto the hydrated salt (sodium acetate trihydrate). Because the liquidis supersaturated, this makes the solution crystallize suddenly whichreleases the energy of the crystal lattice.

Yet another example of use in the heating layer 36 may include the useof a hot gel containing a supersaturated solution of a salt. Heat may begenerated when the crystallization of the given salt occursexothermically. Such heating layer 36 ma be reused by forcing the saltback into solution within the heating layer 36.

Yet other examples for incorporation into the heating layer 36 may alsoinclude the use of high specific heat capacity materials which may heheated, e.g., by placement in a microwave prior to use, and then allowedto release the heat over a specified period of time.

Although the application of heat energy from the treatment strips isdescribed, other variations may alternatively include the application ofusing the treatment strips for cooling of the underlying skin. Ratherthan using the heating layer 36 in an exothermic reaction, the layer maybe configured to utilize an endothermic reaction instead to provide forcooling of the skin at temperatures ranging, e.g., from about 0° C. to37° C. or more particularly from about 25° C. to 35° C. One example mayinclude having the layer 36 to incorporate water and ammonium nitrate orammonium chloride. Mixture of the water and the ammonium may reduce thetemperature of layer 36. Another variation may include the use ofcooling gel made by adding hydroxyethyl cellulose or vinyl-coated silicagel which may be cooled or frozen prior to use. Alternatively, coolingmay be achieved by application of a cooling element such as a Peltierjunction. Cooling, rather than heating, may be applied for conditionssuch as reducing inflammation, alleviating allergies or tired eyes, etc.particularly as the patient rests or sleeps. One example includestreatment for allergic conjunctivitis where application of the coolingtreatment may provide relief from any burning or itching sensations byserving as a vasoconstrictor to limit blood flow, reduce blood vesselleakage and permeability thereby reducing acute swelling andinflammation. Yet another example includes reducing inflammation andfibrosis of a conjunctival bleb resulting from a trabeculectomy ormitigating inflammation generally following any ophthalmic surgicalprocedure.

Given the multitude of various mechanisms for incorporating a heatinglayer 36, the treatment strips may be configured to he single-usedisposable strips, multiple-use disposable, re-usable strips,selectively actuatable, etc.

Aside from the application of heat energy from the treatment strips, thestrips may also include a layer for the diffusion or release of one ormore pharmaceutical, biological, or chemical agents either alone or incombination with the heat treatment. For instance, the pharmaceutical,biological, or chemical agents may he incorporated into the either thecontact layer 34, insulative layer 38, or in a separate layer entirely,for transdermal delivery to the meibomian glands or to the areassurrounding the meibomian glands for additional and/or alternativetreatments. For instance, examples of some of the variouspharmacological agents which may be incorporated into the treatmentstrips (for use with or without the heat treatment) may include, but arenot limited to, anti-inflammatory compounds, antibiotics, topicaltetracycline, oral tetracycline, topical corticosteroids, oralcorticosteroids, topical androgens, metronidazole, steroid antagonists,topical androgen analogues, TGF-β, omega 3 or omega 6 compounds,vasoconstrictors such as naphazoline, oxymetazoline, phenylephrine, andtetrahydrozoline, enzymes that promote lipid production, agents thatstimulate production of enzymes that promote lipid production, agentsthat act as a secretagogue to enhance meibomian gland secretion, agentsthat replace or promote production of any tear component, cholinergic,muscarinic, or nicotinic agonists may be used, cosmeceuticals such asretinol or hyaluronic acid (HA) for wrinkled, puffy, or sagging skin inthe cosmetics space, retinoic acid for acne, or agents that degrade orbreak down lipids like lipases, etc.

Other agents may include, e.g., alpha-melanocyte-stimulating hormone oradrenocorticotropic hormone or androgens like testosterone to increasetear production, agents which stimulate the underlying muscles like theorbicularis oculi or muscle of Riolan to stimulate blinking, increasefrequency of blinking, or maintain longer closure after a blink byinhibiting the levator palpebrae muscle to force a blink or eyelidclosure or otherwise mechanically compress the meibomian glands orglands of Zeis or other goblet cells or accessory lacrimal glands.

Additionally and/or alternatively, other agents for incorporation intothe treatment strips may further include, e.g., neurotransmitters,noxious or irritating chemicals or vapors, hormones, oils, lipids, polarlipids. or fatty acids. Use of neurotransmitters may allow forstimulation to occur via second messenger pathways like activation ofthe Calcium/Protein Kinase C pathways, G-Protein activation, othercalcium related pathways, calcium-calmodulin dependent protein kinases,the cyclic adenosine monophosphate dependent pathways, adenylyl cyclasepathways, inhibition of cAMP dependent phosphodiesterases.

In the event that the pharmacological or chemical agent is releasedduring the heat treatment, the heat may help to improve penetration ofany drugs into the underlying skin.

Yet another variation may incorporate a treatment strip which applies aheat rub that can be applied via the treatment strips onto the upper ULand/or lower eyelids LL for the treatment of the meibomian glands orwhich applies a compound which attracts light and heats up accordingly.Each of these variations may allow for the treatment strips 10, 12 to beapplied and used while allowing for natural blinking to occur tofacilitate the clearing of the ducts of melted oil blockages within themeibomian glands and to facilitate the spreading of the oil onto thetears.

While the treatment strips may incorporate various layers into thestrips to effect various different treatments, the strips may also bevaried in size, shape, contour, etc. depending upon the desiredtreatment areas so long as the treatment strips are contoured or shapedto follow the location of at least one meibomian gland. An example ofanother configuration for the treatment strips is shown in the frontview of FIG. 4, which illustrates a contoured thinned strip 40 sized andshaped for placement along the upper eyelid UL. This treatment strip mayhave a contoured lower edge 42 as well as a contoured upper edge 44which follow the positioning of the underlying meibomian glands.Moreover, although the strips 40 are shown placed upon the upper eyelidsUL of both eyes of the patient P, a single strip 40 may be used upon asingle eyelid to selectively treat the particular meibomian glands inthis and other examples shown herein. Additionally, one or both uppereyelids UL may be treated alone or in combination with one or both lowereyelids LL depending upon the desired treatment in this and otherexamples shown herein.

Another variation is shown in the front view of FIG. 5 which shows acontoured thickened strip 50 having a contoured lower edge 52 andcontoured upper edge 54 for placement upon the meibomian glands as wellas the surrounding tissue and glands. In yet other variations, ratherthan utilizing two separate treatment strips, a singular strip may alsobe used which extends over the bridge of the patient's nose.Additionally, the thickened strip 50 may cover the portions of skinfarther proximally away from the eyelid margin to facilitate treatment.Because arterial blood supply to the eyelids proceed from proximal todistal of the eyelid margins, the treatment strip may heat (or cool) theblood supply as it continues to flow towards the eyelid margins. Thisearly heating (or cooling) may provide a therapeutic effect forincreased comfort to the patient, less impact on eyelid function (suchas blinking), and increased safety of application and distance from theocular surface as well as potentially increased efficacy allowing formore total heating or cooling therapy.

FIG. 6 shows yet another variation having, a contoured thinned strip 60where the lower 62 edge and upper edge 64 converge to a tapered end 66for placement upon the meibomian glands. FIG. 7 shows yet anothervariation where the treatment strips may comprise straightened strips 70having a first width used in combination with a thinned straightenedstrip 72 as well. The straightened strips 70 may comprise straightenedstrips (having optionally rounded corners) which may be selectivelyplaced over the meibomian glands. In this example, a single straightenedstrip 70 may be applied upon the upper eyelid UL of a single eye whilethe remaining eye may utilize a single straightened strip 70 appliedalong a first portion of the upper eyelid UL and a second straightenedstrip 72 having a relatively thinner width for placement upon a secondportion of the upper eyelid UL. Each of the strips may be appliedsingularly or in various combinations depending upon the desiredtreatment areas and are shown in this variation as an exemplarycombination.

In the variation of FIG. 8, an example of contoured thinned strip 80 isshown applied along the lower eyelid LL. As illustrated, the contouredupper edge 82 and contoured lower edge 84 may he contoured to followover the underlying meibomian glands. As described above, the treatmentstrips may be applied singularly over one or both eyes or they may beapplied in combination with treatment strips applied over one or botheves of the upper eyelids. Moreover, any of the treatment strips shownherein may be used in any number of combinations with one another.

FIG. 9 shows another variation where the contoured thickened strip 90may be applied over the lower eyelids LL and may further have a widthwhich is relatively wider than those treatment strips shown above inFIG. 8. Similarly, FIG. 10 shows yet another variation where thecontoured thickened strip 92 may have a width which is relatively widerstill for treating not only the underlying meibomian glands but also anyglands and tissue surrounding the peri-orbital region. As describedabove for the variation of FIG. 5, the widened treatment strip may heat(or cool) the blood supply as it continues to flow towards the eyelidmargins. The early heating (or cooling) may provide a therapeutic effectfor increased comfort to the patient, less impact on eyelid function(such as blinking), and increased safety of application and distancefrom the ocular surface.

Aside from variations in width of the treatment strips, any of thetreatment strips may be varied in length as well to selectively targetportions of the meibomian glands or particularly selected meibomianglands. For example, FIG. 11 shows one variation where the shortenedcontoured strip 100 having a first shortened length may be applied uponthe lower eyelid LL (and/or upon the upper eyelid UL). A secondcontoured strip 102 having a second length which is longer than theshortened contoured strip 100 may also be seen for comparison. FIG. 12similarly shows a shortened and straightened strip 110 applied upon thelower eyelid LL and a second straightened strip 112 having a relativelylonger length applied upon the second lower eyelid LL. The straightenedstrips 110, 112 may incorporate rounded ends and may be varied in lengthdepending upon the desired treatment area. They could also be rounded orcircular to cover one or more styes.

FIG. 13 shows yet another variation where the contoured strips 120 mayhe configured to have tapered ends for overlying the meibomian glands.In comparison, thickened contoured strip 122 is also illustrated havingtapered ends yet is relatively wider to alter the treatment area.

FIG. 14 shows another variation where the contoured strip 130 may have afirst portion 132 which is relatively wider than a second portion 134for placement over the meibomian glands of the lower eyelid LL. Each ofthe first 132 and second portions 134 may be varied in width againdepending upon the desired treatment areas. Another example is shown inFIG. 15 which shows a contoured strip 140 having a first portion 142 andsecond portion 144 which are considerably wider for treating not onlythe meibomian glands along the lower eyelid LL but also the surroundingperi-orbital tissue regions such as the underlying maxillary sinus. FIG.16 shows yet another example of a contoured strip 150 having a firstportion 152 and a second portion 154 which is wider than the firstportion 152 and where the strip 150 is positioned to cover just aportion of the meibomian glands along the lower eyelid LL but alsocovers various other glands, such as the lacrimal glands, around theperi-orbital regions.

FIG. 17 shows yet another variation of a treatment strip comprised of acontoured strip 160 having a secondary enlarged portion 162 attached viaa connecting strip 164. While the contoured strip 160 may treat themeibomian glands along the lower eyelid LL, the secondary enlargedportion 162 may treat region of the tissue along the cheeks of thepatient.

In yet another variation, FIG. 18 shows an example where both an uppercontoured strip 170 and a lower contoured strip 172 may be applied,respectively, along the upper eyelid UL and lower eyelid LL. Asdiscussed previously, the contoured strips 170, 172 are shaped andapplied to follow the underlying meibomian glands while enabling thepatient P to blink normally. FIG. 19 shows a similarly applied uppercontoured strip 180 and lower contoured strip 182 where the strips maybe varied in color to more closely match a skin tone or shade of thepatient P. Because the treatment strips may be used throughout the dayfor any given period of time, the strips 180, 182 may be made in variouscolors or tones to either more closely match the skin tone or shade ofthe patient P.

In yet another variation, FIG. 20 shows another example where thetreatment strips may be varied in length to treat specific regions alongthe upper UL or lower eyelids LL. In this example, a first upper strip190 having a first length may be applied adjacent to a second upperstrip 192 having a second longer length. Optionally, a third upper strip194 and/or fourth upper strip 196 having lengths which are relativelyshorter may also be applied as well over selected meibomian glands. Alower strip 198 having enlarged distal ends 200, 202 are also shown forplacement along the lower eyelid LL. The distal ends 200 may be shapedto facilitate the placement and/or removal of the strip 198 from theskin (or for better adhesion). Yet another example is shown in FIG. 21which illustrates several shortened treatment strips, e.g., first upperstrip 210 and second upper strip 212, placed selectively along the uppereyelid UL along with, e.g., first lower strip 214 and second lower strip216, placed selectively along the lower eyelid LL. Each of the stripsmay be varied in length as well as size depending upon the treatmentarea.

With the lengths of the treatment strips being, variable, multiplestrips may be applied adjacent to one another or to overlap horizontallyand/or vertically along the eyelids. Moreover, one or more of thetreatment strips may be made as a single unit or as a series of panelseither horizontally or vertically oriented which may be optionallyconnected by a backing that is flexible. As shown in the variation ofFIG. 22, each of the targeted strips 220 may have a length of, e.g.,about 1 mm, to cover as few as a single meibomian gland. One or more ofthe targeted strips 220 may be applied along the upper eyelid UL and/orlower eyelid LL. Additionally, one or more of the targeted strips 222may further comprise a connecting member 224 which functions as abacking to couple each of the individual targeted strips 222 to oneanother. The individual strips may be applied selectively atparticularly problematic meibomian glands either along the upper eyelidUL and/or lower eyelid LL. For example, FIG. 23 illustrates theindividual targeted strips 222 placed along just the lower eyelid LL.

While the treatment strips may be applied to one or more of themeibomian glands, variations of the strip may also be used to treatother glands such as the sebaceous glands, e.g., for acne treatment.Treatment strips used to treat acne may utilize differentpharmacological treatments. Other glands in the underlying eyelids andconjunctiva CN for treatment may also include treatment of e.g., theglands of Zeis GZ, goblet cells, accessory sebaceous glands, accessorygoblet cells such as the Henle and Manz glands, accessory lacrimalglands of Wolfring GW or Krause GK, or either one or both lobes of themain lacrimal glands such as the palpebral portion or the orbitalportion.

Moreover, the treatment strips may be used to potentially treat eyedisorders beyond meibomian gland dysfunction including, e.g.,blepharitis, sjogren's syndrome, dacryoadenitis, conjunctivitis,allergic conjunctivitis, keratoconjunctivitis sicca, keratitis,dacryocystitis, iritis, keratitis, retinitis, sclerokeratitis, uveitis,contact lens related eye problems, post blepharoplasty or eyelid, or eyesurgical procedures (e.g., cataract surgery, LASIK, PRK, etc.), absentor dysfunctional blinks disorders, conjunctivitis, blepharospasm,exposure keratopathy, lagophthalmos, lid myokymia, infections, styes,chalazion, hordeolum, glaucoma, blebs, trauma, etc.

Yet another example, as mentioned above, may include use of thetreatment strips for treating disorders of the lacrimal gland LG and/orpalpebral lacrimal gland PL which are located above the eye as shown inFIG. 24. Variously sized treatment strips, such as lacrimal gland strips230 shown in FIG. 25 which is sized to have a curved, upper periphery,may be sized for placement directly over the skin surface above were thelacrimal glands LG are located. Other variations are shown in FIG. 26which illustrates lacrimal gland strips 232 which are relatively thinnerin width as well as in FIG. 27 which illustrates lacrimal gland strips234 which have curved, peripheries ending in tapered ends. The treatmentstrips may deliver heat, e.g., to stimulate the lacrimal gland LG,increase gland metabolism, activity, lacrimation, etc. Alternatively,the treatment strips may deliver cooling therapy to reduce inflammationwhich impairs gland function.

The lacrimal glands LG and/or palpebral lacrimal gland PL may be treatedalone or in combination with the treatment strips contoured fortreatment of the meibomian glands. One variation is shown in FIG. 28which illustrates contoured strips 240 which are enlarged in width tocover both the lacrimal glands LG as well as the meibomian glands alongthe upper eyelid UL. Contoured treatment strips 242 are also shownplaced along the lower eyelids LL for treatment of the meibomian glandsas well.

FIG. 29 shows another variation where lacrimal gland strips 250 may beplaced over the lacrimal glands LG in combination with an integralcombined contoured strip 252 which is sized to encircle the eyesentirely while following the location of the meibomian glands along boththe upper eyelids UL and lower eyelids LL. This fully encircling designmay also be held in place more tightly against the skin with a strapwhich may encircle the patient's head, if so desired. Another variationis shown in FIG. 30 which illustrates an integral combined contouredstrip 260 which is also sized to encircle the eyes entirely and furtherhaving a width suitable for placement over the lacrimal glands LG.

The lacrimal gland strip 270 may be used in combination with any of thetreatment strips shown herein. Another example is illustrated in FIG. 31which shows lacrimal gland strip 270 used in combination with theindividual strips 222 while FIG. 32 shows yet another example wherelacrimal gland strip 270 may be used in combination with not only theindividual strips 222 but also the strips 220 located along respectivelower eyelid LL and upper eyelid UL.

While the treatment strips may be applied over the meibomian glands toapply the heat energy, the treatment does not require the application ofany external force applied by the strip or any other external device butmay utilize the natural blinking of the patient to facilitate treatment,as described above. However, in additional variations, the treatmentstrips may be configured to apply both the heat treatment as well as anexternal force. Any number of mechanisms may be utilized to apply apinching or biasing force to provide for compression of the underlyingskin and of the meibomian glands during application of the heat therapy.One example is shown in the front view of FIG. 33 which illustrates abiased treatment strip 280 which may be comprised of a strip 282, aspreviously described, having one or more biasing mechanisms 284positioned along the strip 282. The one or more biasing mechanisms 284may be positioned along either the upper strip or lower strip or both,as shown.

In this example, the biasing mechanism 284 may locally squeeze orcompress the underlying skin to apply a pressure to the meibomian glandsMG to facilitate the clearing of any obstructions, particularly ifapplied simultaneously with the heat treatment. An example of a biasingmechanism 284 is illustrated in the perspective view of FIG. 34 whichshows how the biasing mechanism 284 may generally comprise portions ofthe strip 282 or separate members biased to form corresponding channels286 which are configured to flex in an open or closed configuration.When the strip is initially placed upon the skin, the ends of the stripmay be pulled to open the channels 286 which may then be placed upon theskin surface. As the strip and biasing mechanisms 284 relax, theunderlying skin and meibomian glands MG may be compressed or pinched bythe compression forces 288 induced into the biasing mechanism 284.

Aside from a compression force, the strip may be formed with alternativecomponents such as a mechanical component to impart vibrational energyto facilitate the expression of the meibomian glands and promote oilsecretion. An example is illustrated in FIG. 35 which shows anothervariation of the contoured strip 290A, 290B having one or more vibratingelements 292 (e.g., piezoelectric transducers, electromagneticactuators, eccentrically coupled rotating elements, etc.) incorporatedalong the strips 299A, 290B. The one or more vibrating elements 292 maybe electrically coupled to a power supply and/or processor 294 alsocontained along the strips 290A, 290B. Moreover, the vibrational energymay he imparted separately from heat treatment or in combination withthe heat therapy. The power supply may include a micro-battery which canbe rechargeable to deliver microcurrents of energy.

Aside from the application of mechanical pressure or vibrational energy,other forms of energy may also be delivered by one or more of thetreatment strips. Another variation is illustrated in FIG. 36 whichshows an upper contoured strip 300A having a conductive element 302 suchas a wire integrated along the entire length (or a partial length) ofthe contoured strip 300A. The conductive element 302 may be configuredin an alternating pattern or it may be simply aligned along the lengthof the strip as shown by conductive element 306 (or electricallyresistive) along the lower contoured strip 300B. Each of the conductiveelements 302, 306 may be in electrical communication with a respectivepower supply and/or processor 304, 308. The conductive elements 302, 306may be selectively actuated to apply either heat energy or they mayconfigured to apply radio-frequency (RF) energy to the underlying skinand meibomian glands. With respect to the application of electricalenergy, one form of electrical energy applicable by the treatment stripsmay include use of a transcutaneous electrical nerve stimulationfeature, e.g., to deliver neural stimulation to increase tearproduction. The conductive elements may generate the thermal energy viavarious power sources, e.g., battery, solar cell, kinetic movement, RF,etc.

FIG. 37 shows yet another variation where the contoured strips 310A,310B may be configured to incorporate an electrode or antenna 312coupled to a power supply and/or processor 314 for applying, e.g.,microwave energy to the underlying meibomian glands. Aside from theelectrical or microwave energy, the treatment strips may be configuredto apply yet other forms of energy for treating the meibomian glands.For example, other variations may incorporate actuators or transmittersfor applying ultrasonic, RF, microwave, magnetic, photonic (light energyin the infrared or visible light spectrum), etc. In yet othervariations, the conductive elements may be configured to function aselectromagnetic elements once actuated or the strips may incorporateferromagnetic elements to promote closure of the eyelids. The magneticforce could serve to squeeze the meibomian glands and express the oilyobstruction as the eyes are opened and re-opened when overcoming themagnetic force.

In yet another variation, one or both treatment strips 320A, 320B may beconfigured to incorporate an indicator 324, e.g., LED light, alarm,vibration element, etc., electrically coupled to a power supply and/orprocessor 322 to alert the patient when a prescribed treatment has beencompleted. This feature (and any of the other features) may be combinedwith any of the other variations of the treatment strips describedherein as practicable.

FIG. 39 shows vet another variation where the eyelid treatment system330 may be formed into a coupled dual-strip design, e.g., a “wishbone”design, where the dual-strip heating strips may have two heatingelements which follow the location of the meibomian glands the upper ULand lower LL eyelid of a single eye. Depending upon whether both eyes ora single eye and/or both upper and lower eyelids are treated, the system330 may comprise a first heating strip assembly 332 and a second heatingstrip assembly 334 for each respective eye. Each of the assemblies 332,334 may accordingly utilize an upper and a lower lid treatment heater,e.g., upper lid treatment strip 332A and lower lid treatment strip 332B,where each of the upper and lower elements may be coupled to one anothervia wires 336. Moreover, each of the assemblies 332, 334 may be coupledvia a connecting cable 338 to controller 340 which may be coupled (e.g.,through an input/output port such as a headphone jack, USB port, orother connection port) to a portable electronic device 342 (e.g.,smartphone having a touch screen interface, tablet, PDA, laptopcomputer, etc.) as shown.

In other variations, the number of connecting cables may range anywherefrom 1-4 connector cables rather than utilizing a single cable 338. Forinstance, one cable may be used to provide power and communication to afew or all four heating elements in each of the assemblies 332, 334.Alternatively, four connecting cables may provide power andcommunication to each of the heating elements in assemblies 332, 334.Yet in other alternatives, two connecting cables may provide power andcommunication to each of the assemblies 332, 334.

In other additional variations, any of the treatment strips describedmay be used in combination with the controller 342 described herein, aspracticable. Yet in a further variation, oval or circular shaped heatingelements may covers the eye and both eyelids where an outer border ofthe heating elements or strips may follow the path of the upper andlower meibomian glands. In this case, one treatment strip may cover botheyelids and both sets of meibomian glands and the user may use a totalof two (rather than four) round, circular, or oval shaped treatmentstrips to cover both eyes. Such a variation may be used, e.g., for anight time therapy in bed prior to or during sleep when the eyes neednot necessarily be open.

The assemblies 332, 334 may generally comprise strips, as previouslydescribed, which follow the location of the meibomian glands while stillallowing patients to blink easily and proceed in comfort with dailyactivity. An example of such heaters which may be configured for usewith the treatment system 330 may include thin, flexible heaters whichare commercially available through companies such as Minco Products,Inc. (Minneapolis, Minn.) or can be custom designed and manufacturedindependently or through third party manufacturing. Each individualtreatment strip, e.g., treatment strips 332A, 332B, may each be sizedfor a single eyelid, e.g., 28 mm×7 mm×0.15 mm, having a bottom chordlength of, e.g., 28 mm, with a radius of curvature of, e.g., 75 mm, andhaving a general configuration of an arcuate rectangle having blunted,corners where the nasal or temporal edges may coincide with the radii ofthe arc. However, these size limitations are intended to be exemplaryand not limiting since the treatment strips 332A, 332B may be sized tobe smaller or larger to accommodate different eye anatomies.

Moreover, the individual treatment strips 332A, 332B may be formed asthin, flexible transparent polymers containing the heating elementswhile the contact surface of the strips may be affixed to the respectiveeyelids with, e.g., a disposable adhesive. Other variations may utilizeopaque or colored strips, e,g., skin-tone colors. Moreover, one or moretemperature sensors may also be integrated into the treatment stripswhere the heating elements and sensors may be routed through theconnecting cable 338 to a power source and/or controller 340 and/orportable electronic device 342, as shown.

Controller 340 may generally comprise a hardware/software platform orunit which may be programmed for controlling the therapy treatments.Accordingly, the controller 340 may include a processor as well as apower supply such as a battery (rechargeable or disposable) forproviding power to the assemblies 332, 334. The power supply withincontroller 340 may be optionally rechargeable separate from the portableelectronic device 342 or the power supply may draw power for theassemblies 332, 334 and processor directly from the portable electronicdevice 342 as well.

In the case where the controller 340 is programmed to provide thetherapy treatment protocols, one or several controls for controlling thetreatments may be built directly into controller 340. The portableelectronic device 342 may interface with the controller 340 to display,in one variation, part of the controls on a screen (e.g., touchscreen)of the electronic device 342 such as controls for starting and/orstopping a treatment. Alternatively, all of the controls may reside onthe controller 340 while a display on the electronic device 342 mayserve primarily to show or track various results or treatmentparameters.

In yet another alternative, the all of the controls may reside on thedisplay of the electronic device 342 for controlling the varioustreatment options and parameters rather than on the controller 340. Inthis variation, the electronic device 342, in this example a smartphone,may also provide the power to the treatment strip assemblies 332, 334and may also control the various treatment temperatures and times aswell as provide temperature feedback or other physiological parameterswhich may be measured. In this case, the treatment strips 332, 334 andconnecting cable 338 may be plugged directly into the mobile or portableconsumer electronic device 342. For instance, the electronic device 342may be used to display treatment parameters and controls such as an iconor button for initiating therapy. In one example, therapy may beinitiated by the user through electronic device 342 to heat one or moreof the strips of one or both of the treatment strip assemblies 332, 334.In any of the variations, the electronic device 342, particularly in thecase of a smartphone or tablet, may have an optional program orapplication downloaded onto the device which facilitates the variouscontrol and/or display parameters on the electronic device 342 dependingupon how the electronic device 342 is used with the controller 340 andassemblies 332, 334.

Additionally, the electronic device 342 may also provide a diagnosticfunction to allow the user to test for dry eye and/or to determine howtreatment is progressing either before, during, or after treatment.Accordingly, the electronic device 342 or controller 340 may leverage,e.g., an integrated camera and/or flashlight source, for purposes ofimaging the user's ocular tear film or ocular surface and evaluatingcommonly used tear assessment criteria such as total tear film layerthickness, and/or tear film mucin layer thickness, and/or tear filmlipid layer thickness, and/or tear film aqueous layer thickness, or anycombination thereof. In addition to imaging of the user's tear filmand/or ocular surface conditions, the mobile application may includeother common methods for diagnosing dr y eye such as user questionnairesrelated to the user patient's symptoms, discomfort, and/or improvementor worsening of symptoms that can be completed using the electronicdevice's touch screen interface, results stored on the electronic device342 or web application or manufacturer's servers, tracked over time fortrend evaluation, and possibly shared with the user's physician.

Moreover, in an of the variations, the controller 340 and/or electronicdevice 342 may be programmed or initiated to heat up the assemblies 332,334 to, e.g., 42.5° C.+/−1° to 2° C. Treatment time may be set to, e.g.15 to 30 minutes, and the controller 340 and/or electronic device 342may further be programmed to shut down when the allotted treatment timehas passed or if the measured temperature rises above a predeterminedlevel, e.g., 45° C. Additionally, the controller 340 and/or electronicdevice 342 may also be programmed or set to indicate various treatmentparameters (e.g., the initiation of treatment, warming of the heatingelements, completion of treatment, errors, battery life, etc.) throughany number of visual, auditory, or haptic indicators.

Additionally, the controller 340 and/or electronic, device 342 may beused to store and/or transmit various data such as historical treatmentdata, usage time, total treatment time, temperature data, etc.Furthermore, the controller 340 and/or electronic device 342 maycommunicate wirelessly with a remote server or additional controller,allowing the controller 340 and/or electronic device 342 to also beprogrammed remotely, e.g., by a physician or other party. In yet othervariations, audio and/or visual information (e.g., advertisements orother media) may also be displayed upon the controller 340 and/orelectronic device 342 which may be received from remote servers orvarious other data may be transmitted to and/or from the controller 340and/or electronic device 342 as well.

In yet other variations, although controller 340 is illustrated as beingcoupled to assemblies 332, 334 via a wired connecting cable 338, othervariations may have controller 340 wirelessly connected with assemblies332, 334. Such a connection may be through any number of wirelessprotocols such as Bluetooth®, RF, etc.

This “precision temperature control” mobile heating therapy system maybe used for heating other parts of the body as well, where the systemremains nearly the same, but the heating element dimensions may bevaried and power requirements may also be changed depending on the totalsurface area being treated and temperature goals.

With the incorporation of a processor into the treatment strips,treatment times or other parameters such as temperature of the stripsmay be programmed and optionally shut on or off selectively by thepatient or automatically. Moreover, other parameters such as thefrequency of the heat delivery or other stimulation may also beprogrammed by the processor to provide further flexibility in treatment.

The applications of the devices and methods discussed above are notlimited to the treatment of dry eye syndrome but may include any numberof further treatment applications. Moreover, such devices and methodsmay he applied to other treatment sites within the body where acute orchronic inflammation causes a disease or condition. The treatment stripscan be accordingly custom-designed to follow the path of the underlyingphysiology, e.g., custom designed and contoured cooling or heatingtreatment strips to treat the sinuses and acute or chronic sinusitis,respectively, rhinitis and allergic rhinitis, joint aches andinflammation, arthritis, muscle aches, back pain, headaches, wounds,sports injuries, etc. Modification of the above-described assemblies andmethods for carrying out the invention, combinations between differentvariations as practicable, and variations of aspects of the inventionthat are obvious to those of skill in the art are intended to be withinthe scope of the claims.

What is claimed is:
 1. A treatment system for dry eye syndrome,comprising one or more strips configured to adhere to an underlyingregion of skin in proximity to one or both eyes of a subject such thatthe one or more strips allow for the subject to blink naturally withoutrestriction from the one or more strips; and a controller incommunication with the one or more strips, the controller beingprogrammable for a treatment therapy, wherein the one or more strips areconfigured to emit energy to the underlying region of skin, and whereinthe one or more strips are shaped to follow a location of one or moremeibomian glands contained within the underlying region of skin.
 2. Thesystem of claim 1 wherein the energy comprises thermal energy.
 3. Thesystem of claim 1 wherein the one or more strips comprise a contactsurface for placement against the region of skin.
 4. The system of claim1 wherein the one or more strips comprise a heating layer in thermalcommunication with the region of skin.
 5. The system of claim 4 furthercomprising a thermochromic layer in thermal communication with theheating layer.
 6. The system of claim 1 wherein the one or more stripseach have a first curved or arcuate periphery which is shaped to extendand follow a border of the one or more meibomian glands and a secondcurved or arcuate periphery which is shaped to extend and follow a freemargin of an upper or lower eyelid.
 7. The system of claim 1 wherein thecontroller is coupled to the one or more strips via a connecting cable.8. The system of claim 1 wherein the controller is programmed to controlone or more parameters of the one or more strips.
 9. The system of claim1 wherein the one or more parameters comprise a temperature, treatmenttime, frequency of treatment, or thermal profile of the one or morestrips.
 10. The system of claim 1 further comprising a portableelectronic device removably coupled to the controller.
 11. The system ofclaim 10 wherein the portable electronic device comprises a smartphoneor tablet.
 12. The system of claim 11 wherein the smartphone isprogrammed to provide an auditory, visual, or haptic indicator forcommunicating with the user.
 13. A method of treating dry eye syndrome,comprising: adhering one or more strips to a region of skin in proximityto one or both eyes of a subject such that the one or more strips allowfor the subject to blink naturally without restriction from the one ormore strips; initiating a treatment to the region of skin with the oneor more strips via a controller in communication with the one or morestrips, emitting energy from the one or more strips to the region ofskin, wherein the one or more strips are shaped to follow a location ofone or more meibomian glands contained within the region of skin. 14.The method of claim 13 wherein adhering comprises positioning the one ormore strips in proximity to one or both eyes such that a first curved orarcuate periphery of the one or more strips extends and follows a borderof the one or more meibomian glands and a second curved or arcuateperiphery of the one or more strips extends and follows a free margin ofan upper or lower eyelid.
 15. The method of claim 13 wherein adheringcomprises placing a contact surface of the one or more strips againstthe region of skin.
 16. The method of claim 13 wherein emitting energycomprises applying thermal energy from a beating layer in the one ormore strips to the underlying region of skin.
 17. The method of claim 13wherein initiating comprises programming the one or more strips via acontroller attached to the one or more strips.
 18. The method of claim17 wherein programming comprises controlling one or more parameters ofthe one or more strips,
 19. The method of claim 17 wherein controllingcomprises controlling a temperature, treatment time, frequency oftreatment, or thermal profile of the one or more strips.
 20. The methodof claim 13 wherein initiating further comprises displaying at least oneparameter on a portable electronic device removably coupled to thecontroller.
 21. The method of claim 20 further comprising interfacingwith a touch screen interface of the electronic device.
 22. The methodof claim 20 further comprising wirelessly communicating with theelectronic device with a remote server.